AB0652 HISTOLOGICAL RENAL FEATURES AND CYTOKINES ASSESSMENT AS POSSIBLE BIOMARKERS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND LUPUS NEPHRITIS
Authors: V. Varriano, C. DI Mario, A. Paglionico, L. Petricca, M. R. Gigante, B. Tolusso, E. Gremese
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Lupus Nephritis (LN) management remains a challenge for the inadequacy of the traditional parameters in identifying more severe disease and preventing renal damage. <h3>Objectives</h3> To identify a multipanel biomarkers matrix, from histological to molecular level, aiming to improve prognostic stratification and therapeutic protocol of LN patients. <h3>Methods</h3> 45 SLE patients with active disease (age: 40.5 ± 11.0 years) at disease onset or at disease flare were enrolled. 6 patients with LN in persistent remission (R-LN) (age: 43.5 ± 11.9 years) were included as controls. 28 patients had an active LN and underwent ultrasound-guided renal biopsy while 15 patients with non-renal SLE (NR-SLE) displayed cutaneous or articular manifestations. Laboratory, immunological and disease activity data were collected at baseline and then at 6(T6) and 12(T12) months. Renal biopsies were evaluated according to ISN/RPS classification, assessing the activity and chronicity indexes and the active interstitial infiltrate (II) using the BANFF score system. Serum level of BAFF, IL-2, L-6, IL-17 and IFN-α were assayed in the study cohort by ELLA panel at each timepoint. <h3>Results</h3> Considering LN cohort, 66% of the renal biopsies belonged to class III and IV; 71.8% of LN patients had a II&gt;5%. Performing univariate analysis for each renal outcome, focusing on histological assessment, a significant association between higher activity index and worse renal prognosis in terms of remission achievement at 12 months (<i>p= 0,04</i>), proteinuria and chronic renal damage development (<i>p= 0,04</i> and <i>p= 0,03</i> respectively) was observed. Through the ROC curve analysis, a cut-off value of activity index of 7.5 was identified (sensitivity 72.7%, specificity 66.7%) [AUC: 0.77; 95% CI, 0.56-0.98; p= 0.04] for remission achievement within 12 months and proteinuria development. Furthermore, LN patients with presence of II&gt;5% were not only less likely to achieve early remission (<i>p= 0,04</i>) as well as those with at least one antiphospholipid antibody (ApL) positivity (<i>p= 0,05</i>), but displayed a worse renal outcome overall, though without reaching statistical significance. The analysis of circulating cytokines revealed that serum levels of IL-6 were significantly higher in patients with active disease as compared to R-LN patients, independently from renal involvement (LN: 7.6 ± 10.0 vs R- LN: 2.1 ± 2.1, <i>p=0.02</i>; NR-SLE: 11.4 ± 17.8 vs R-LN: 2.1 ± 2.1, <i>p=0.02</i>). Moreover, baseline serum level of IFNα was significantly increased in LN patients compared to R-LN (12.1 ± 36.8 vs 1.5 ± 3.6, <i>p=0.01</i>). Serum levels of IL-6 in LN patients positively correlated with disease activity index (R=0.819; p&lt;0.001), and negatively with C3 (R= -0.608; p=0.003) and C4 (R= -0.675; p=0.01). Furthermore, serum levels of IL-6 were associated with histological severity being significantly higher in patients with II&gt;5% (<i>p= 0.01</i>) and positively correlating with activity index (R=0.695; <i>p=0.01</i>). The evaluation of cytokines serum levels in relation to outcome achievement revealed that NR-SLE patients with favorable course had baseline higher serum level of IL-2 than those with active disease (0.6 ± 0.2 vs 0.1 ± 0.1, p=0.01). Finally, LN patients with higher serum levels of IL-6 during the follow-up were less likely to reach remission (3.7 ± 1.8 vs 2.1 ± 1.4, p=0.02) as well as LN patients with higher serum level of IL-17 (3.4 ± 8.0 vs 0.9 ± 0.3, p=0.01<i>).</i> In particular, higher baseline serum levels of IL-17 were observed in patients who developed persistent proteinuria than those who did not (2.3 ± 2.3 vs 0.7 ± 0.5, p=0.02) and tended to remain higher also during FU, together with IL-6 serum level. <h3>Conclusion</h3> II&gt;5%, higher disease activity index and Apl+ represent in our study the strongest predictors of worse renal outcome, among traditional parameters. Higher IL-6 and IL-17 serum levels, at baseline and during FU, emerge as negative prognostic factor suggesting a possible role as biomarkers of more aggressive LN. IL-2 seems to have a protective role in extra renal disease. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.